The present application is related generally to methods and apparatus for the detection, analysis, and manipulation of microscopic specimens, and in particular, to methods and apparatus to manipulate, detect, and/or analyze samples such as single molecules, single small particles, or small quantities of matter such as DNA as the samples are passed through a nanoscale gap between detector elements in a nanofluidic channel.
There are great needs to detect, analyze and manipulate single molecules, single small particles and single small samples of matter in various fields such as biology, medicine, and pharmaceutical research. The biological species include DNA, proteins, enzymes, and other bio-molecules which have an extremely small volume. In detection, sometimes a single molecule resolution of a single DNA base pair is needed. Often these molecules and small particles are in solution. Existing devices for measurement and analysis of small bio-molecules such as DNA have limitations. For example, devices which rely upon pulling strands of molecules through nanopores and measuring the ionic current through the nanopore caused by the blockage of DNA suffer from poor confinement of the DNA strand within the nanopore and noise effects caused by the movement of the unrestrained portions of the DNA strand outside of the nanopore. These devices additionally rely upon the DNA blockage of ionic current through the nanopore, which is an electrical signal along the DNA backbone, and which depends both on the DNA base pairs within the nanopore, as well as some DNA base pairs which are outside of the nanopore and are subjected to random movement. As such, these devices may be unable to sufficiently resolve two adjacent DNA bases.
The present invention overcomes certain current limitations and offers unique capabilities and performance, including ultra-fast real-time and label-free analysis (e.g. sequencing) of an individual strand of DNA.